1. Field of the Invention
The present invention concerns a new nucleoside having anti-retrovirus activity. More particularly, the present invention concerns 3'-azido-2',3'-dideoxy-5-halouridine.
2. Background Information
Applicants Tai-Shun Lin and William H. Prusoff heretofore explored the biological potential of the 3'- and the 5'-amino analogues of thymidine ("Synthesis and Biological Activity of Several Amino Analogues of Thymidine", Journal of Medicinal Chemistry, 21, 109, (1978)), wherein 3',5'-diamino-3',5'-dideoxythymidine, 3'-amino-3'-deoxythymidine, 5'-amino-5'-deoxythymidine, 3'-azido-5'-O-p-tolylsulfonyl-3'-deoxythymidine and 3',5'-diazido-3',5'-dideoxythymidine were prepared and evaluated.
In "A Novel Synthesis and Biological Activity of Several 5-Halo-5'-Amino Analogues of Deoxyribopyrimidine Nucleosides", Journal of Medicinal Chemistry, 21, 106, (1978), applicants Tai-Shun Lin and William H. Prusoff reported a synthetic prodedure for the synthesis of 5-chloro, 5-bromo and 5-iodo-5'-amino-2',5'-dideoxyuridine, as well as two analogues, 5-iodo-5'-amino-2',5'-dideoxycytidine and 5-fluoro-5'-amino-2',5'-dideoxyuridine, in good yield.
In "Synthesis and Biological Activity of Various 3'-Azido and 3'-Amino Analogues of 5-Substituted Pyrimidine Deoxyribonucleosides", Journal of Medicinal Chemistry, 26, 1691, (1983) by Tai-Shun Lin, You-Song Gao and William R. Mancini, the following compounds were synthesized and evaluated: 3'-amino-2',3'-dideoxy-5-fluorouridine; 3'-amino-2',3'-dideoxycytidine and 3'-amino-2',3'-dideoxy-5-fluorocytidine.
Hiroaki Mitsuya, Kent J. Weinhold, Phillip A. Furman, Marty H. St. Clair, Sandra Nusinoff Lehrmann, Robert C. Gallo, Dani Bolognesi, David W. Barry and Samuel Broder, "3'-Azido-3'-Deoxythymidine (BW A 509 U): An Antiviral Agent that Inhibits the Infectivity and Cytopathic Effect of Human T-Lymphotropic Virus Type III/Lymphadenopathy--Associated Virus In Vitro", Proc. Natl. Acad. Sci. USA, 82, 7096, (1985) described the use of 3'-azido-3'-deoxythymidine to inhibit HTLV III/LAV replication and to block the cytopathic effects of HTLV III/LAV in vitro.